A novel immunotherapeutic approach improved outcomes for patients with advanced bladder cancer, according to a study published in Clinical Cancer Research (doi:10.1158/1078-0432.CCR-15-1265).

Immunotherapy has emerged recently as a viable and attractive strategy for the treatment of advanced cancer.

“In this study, we assessed whether a novel immunotherapeutic approach that we have devised, called personalized peptide vaccination, could improve outcomes for patients who have advanced bladder cancer that has progressed after platinum-based chemotherapy,” said first author Masanori Noguchi, MD, PhD, of Kurume University School of Medicine in Japan. “This is a disease for which the prognosis is poor; median survival is just 13 to 15 months from the time of starting platinum-based chemotherapy.”

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Noguchi and colleagues enrolled 80 patients with bladder cancer that had progressed after platinum-based chemotherapy in the phase II clinical trial. Patients were randomly assigned to personalized peptide vaccine and best-supportive care (39 patients) and best-supportive care (41 patients). Best-supportive care included palliative radiotherapy, antibiotics, and pain relief.

Noguchi explained that personalized peptide vaccination involved patients receiving 2 to 4 peptides once a week for 8 weeks and then once every 2 weeks for 4 doses. The peptides were selected from a pool of 31 peptides and determined by which human leukocyte antigen (HLA) class IA marker was expressed by the patient’s cancer and whether there were signs of an existing immune response to the peptides in the patient’s blood.

A partial response occurred in 9 patients assigned to personalized peptide vaccine and best supportive care and in none of the patients assigned to only best supportive care, as assessed by RECIST 1.1 criteria. Two of the patients who had a partial response were alive with no disease progression at the time of data cutoff, April 20, 2014.

The median overall survival for patients assigned to personalized peptide vaccine and best supportive care was almost twice as long as that for patients assigned best supportive care: 7.9 months vs 4.1 months.

The median progression-free survival was not significantly different between the 2 groups. Noguchi explained that this might be because personalized peptide vaccination requires time to produce an effective antitumor immune response; in contrast, tumor shrinkage with chemotherapy or small moleculescan be immediate.

“We were excited to see that personalized peptide vaccination led to a significant improvement in overall survival,” said Noguchi. “This suggests that this immunotherapeutic approach might become a treatment option for advanced bladder cancer after failure of platinum-based regimens. However, large-scale, randomized clinical trials are needed to confirm our results.”

Noguchi reported that major limitations of the study including only a small number of patients were enrolled and the study design was not blinded. To address this concern, he said that they are planning a double-blinded, placebo-controlled, randomized phase II study in patients with advanced metastatic urothelial cancer (pelvis, ureter, and bladder cancer) after platinum-based chemotherapy.